Transplantation = Act of transferring cells,

tissues or organs from one site to another.

ORGAN DISEASE
TRANSPLANTED
Kidney End-stage renal failure
Heart Terminal cardiac failure
Lung Pulmonary hypertension, CF
Liver Cirrhosis, cancer
Cornea Dystrophy, keratitis
Pancreas, islets Diabetes
Bone marrow Immunodeficiency, leukemia
Small bowel Cancer
Skin Burns
Transplantation = Act of transferring cells,
tissues or organs from one site to another.

Rejection = Damage done by immune system to

transplanted organ or tissue.
Why are transplanted tissues rejected?

Rejection of transplanted tissues occurs because

immune system of the recipient recognizes and
responds to foreign histocompatibility antigens
expressed on the graft

Major inducers of allogeneic rejection reactions =

= MHC or HLA antigens
Paternal = HLA-A1, B3, C5, DP3, DQ5, DR7
Maternal = HLA-A2, B4, C6, DP4, DQ6, DR8

A2 B3 B4
A1 C5
C6

DR7 DP3
DR8 DP4
DQ5 DQ6
Major inducers of allograft rejection = MHC or HLA antigens

Weaker rejection = Minor H ags  weak 1st set reactions

First set reactions = “Primary” response

Second set reactions = “Secondary” response
GRAFT

AUTOGRAFT ACCEPTANCE
1ST SET REJECTION
2nd SET REJECTION
 2nd SET REJECTION

AUTOGRAFT ACCEPTANCE 1ST SET REJECTION

Allograft vascularized Complete rejection 2nd set rejection
on day 5 on day 12 on day 7
Foreign transplantation antigens

T cells activated

Cytokines produced

Effector mechanisms activated

Graft destruction
 Graft rejection occurs in two stages:

1. The Sensitization stage

2. The Effector stage

In the Sensitization stage, alloreactive lymphocytes

proliferate in response to graft alloantigens;
this involves CD4+ T cells and occurs in lymph nodes.
Sensitization Stage

Th
Th
Th
Th
TDTH
TC

TDTH
 Graft rejection occurs in two stages:
1. The Sensitization stage

2. The Effector stage

In the Effector phase,

stimulated host T cells and macrophages reach the graft;
DTH and CTL reactions (and ADCC) and cytokines attack the graft.

1. T cells are central cells in rejection

2. Macrophages are also important (inflammation)
3. Antibodies are less important, but not unimportant
 Th
Th
Th
Th
TDTH
TC

TDTH

Effector Stage
Sensitization Stage

Th
Th
Th
Th
TDTH
TC

TDTH

Effector Stage
Activated macrophage
Immunological Components of
Graft Rejection
Acute Rejection:
T cell-mediated, days/weeks

Chronic Rejection:
Months/years

Hyperacute Rejection:
Antibody-mediated
 Graft versus Host Disease (GvHD)

• Sort of a reverse of graft rejection

• Graft attacks the host

• When donor immunocompetent lymphoid cells

attack immunocompromised host

• Usually by T cell cytotoxicity

• Diarrhea, skin lesions, jaundice, spleen

enlargement, high mortality rate
 Immunosuppression of Graft Rejection and GvHD
To prevent the senitization of pre-existing mature T cells

General / Non-specific Specific

T cell inhibitors
Cyclosporin

Anti-inflammatory drugs
Corticosteroids

Inhibition of Mitosis
Azathioprine

Lymphoid irradiation
Corticosteroids inhibit presentation

Proliferation

Resting T
APC Activated T

T cell inhibitors inhibit activation

Mitotic inhibitors inhibit proliferation

 Immunosuppression of Graft Rejection and GvHD
To prevent the senitization of pre-existing mature T cells

General / Non-specific Specific

T cell inhibitors
Cyclosporin Monoclonal antibodies to T cells
- Anti-CD3 antibodies
Anti-inflammatory drugs
Corticosteroids - Anti-IL-2 Receptor abs
- Anti-CD4 antibodies
Inhibition of Mitosis
Azathioprine

Lymphoid irradiation